Department of Laboratory Medicine and Pathology, University of Alberta and Cross Cancer Institute, Edmonton, Alberta, Canada.
PLoS One. 2012;7(4):e33738. doi: 10.1371/journal.pone.0033738. Epub 2012 Apr 2.
Fatty acid synthase (FASN), a key player in the de novo synthetic pathway of long-chain fatty acids, has been shown to contribute to the tumorigenesis in various types of solid tumors. We here report that FASN is highly and consistently expressed in mantle cell lymphoma (MCL), an aggressive form of B-cell lymphoid malignancy. Specifically, the expression of FASN was detectable in all four MCL cell lines and 15 tumors examined. In contrast, benign lymphoid tissues and peripheral blood mononuclear cells from normal donors were negative. Treatment of MCL cell lines with orlistat, a FASN inhibitor, resulted in significant apoptosis. Knockdown of FASN expression using siRNA, which also significantly decreased the growth of MCL cells, led to a dramatic decrease in the cyclin D1 level. β-catenin, which has been previously reported to be upregulated in a subset of MCL tumors, contributed to the high level of FASN in MCL cells, Interesting, siRNA knock-down of FASN in turn down-regulated β-catenin. In conclusion, our data supports the concept that FASN contributes to the pathogenesis of MCL, by collaborating with β-catenin. In view of its high and consistent expression in MCL, FASN inhibitors may hold promises for treating MCL.
脂肪酸合酶（FASN）是长链脂肪酸从头合成途径中的关键酶，已被证明参与多种实体瘤的肿瘤发生。我们在此报告，脂肪酸合酶在套细胞淋巴瘤（MCL）中高度一致地表达，这是一种侵袭性 B 细胞淋巴瘤。具体来说，在所有四个 MCL 细胞系和 15 个检查的肿瘤中都可检测到 FASN 的表达。相比之下，良性淋巴组织和来自正常供体的外周血单个核细胞为阴性。用脂肪酸合酶抑制剂奥利司他处理 MCL 细胞系会导致明显的细胞凋亡。用 siRNA 敲低 FASN 表达，也会显著降低 MCL 细胞的生长，导致细胞周期蛋白 D1 水平显著下降。β-连环蛋白先前已被报道在 MCL 肿瘤的亚群中上调，有助于 MCL 细胞中 FASN 的高水平，有趣的是，FASN 的 siRNA 敲低反过来也下调了β-连环蛋白。总之，我们的数据支持 FASN 通过与β-连环蛋白合作促进 MCL 发病机制的概念。鉴于 FASN 在 MCL 中的高表达，脂肪酸合酶抑制剂可能有望用于治疗 MCL。
